Theobromine inhibits differentiation of 3T3-L1 cells during the early stage of adipogenesis via AMPK and MAPK signaling pathways

Jang, Yeon Jeong; Koo, Hyun Jung; Sohn, Eun‐Hwa; Kang, Se Chan; Rhee, Dong‐Kwon; Pyo, Suhkneung

doi:10.1039/c5fo00397k

Cited by 70 publications

(55 citation statements)

References 45 publications

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“…8 Furthermore, recent studies showed that the induction of the cell cycle arrest at the G0/G1 phase suppresses MCE, resulting in the inhibition of adipogenesis. [37][38][39] Here, we also found that ezetimibe could arrest the cell cycle at the G0/G1 phase, which induced the AMPK-dependent inhibition of cell proliferation dependently on AMPK in the early stage of adipogenesis. [37][38][39] Here, we also found that ezetimibe could arrest the cell cycle at the G0/G1 phase, which induced the AMPK-dependent inhibition of cell proliferation dependently on AMPK in the early stage of adipogenesis.…”

Section: Discussionsupporting

confidence: 58%

Ezetimibe ameliorates lipid accumulation during adipogenesis by regulating the AMPK–mTORC1 pathway

et al. 2019

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Adipogenesis, a critical process that converts adipocyte precursors into adipocytes, is considered a potential therapeutic target for the treatment of obesity. Ezetimibe, a drug approved by the United States Food and Drug Administration, is used for the treatment of hypercholesterolemia. Recently, it was reported to ameliorate high fat diet‐induced dyslipidemia in mice and reduce lipid accumulation in hepatocytes through the activation of AMPK. However, the anti‐adipogenic effects of ezetimibe and the underlying molecular mechanism have not yet been elucidated. Here, we found that ezetimibe reduced lipid accumulation via activating AMPK during the early phase of adipogenesis. We also observed that ezetimibe inhibited peroxisome proliferator‐activated receptor γ, which is a major transcription factor of adipogenesis. Furthermore, ezetimibe‐mediated AMPK activation reduced lipid accumulation by inhibiting mTORC1 signaling, leading to the downregulation of lipogenesis‐related genes. Mitotic clonal expansion, required for adipogenesis, accelerates cell cycle progression and cell proliferation. We additionally observed that ezetimibe prevented the progression of mitotic clonal expansion by arresting the cell cycle at the G0/G1 phase, which was followed by the inhibition of cell proliferation. Collectively, ezetimibe‐mediated inhibition of adipogenesis is dependent on the AMPK–mTORC1 pathway. Thus, we suggest that ezetimibe might be a promising drug for the treatment of obesity.

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Section: Discussionsupporting

confidence: 58%

Ezetimibe ameliorates lipid accumulation during adipogenesis by regulating the AMPK–mTORC1 pathway

et al. 2019

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“…has described an inhibitory role for THB on adipogenesis by the murine stromal adipocyte-progenitor cell line 3T3-L1 [42]. This is interesting in the context of the results presented here because the pathways that regulate adipogenesis and osteogenesis in mammalian cells are antagonistic to one another [32, 43–48].…”

Section: Discussionsupporting

confidence: 51%

Theobromine Upregulates Osteogenesis by Human Mesenchymal Stem Cells In Vitro and Accelerates Bone Development in Rats

et al. 2016

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Theobromine (THB) is one of the major xanthine-like alkaloids found in cacao plant and a variety of other foodstuffs such as tea leaves, guarana, and cola nuts. Historically, THB and its derivatives have been utilized to treat cardiac and circulatory disorders, drug-induced nephrotoxicity, proteinuria and as an immune-modulator. Our previous work demonstrated that THB has the capacity to improve the formation of hydroxyl-apatite during tooth development, suggesting that it may also enhance skeletal development. With its excellent safety profile and resistance to pharmacokinetic elimination, we reasoned that it might be an excellent natural osteoanabolic supplement during pregnancy, lactation and early postnatal growth. To determine whether THB had an effect on human osteoprogenitors, we subjected primary human bone marrow mesenchymal stem cells (hMSCs) to osteogenic assays after exposure to THB in vitro and observed that THB exposure increased the rate of osteogenesis and mineralization by hMSCs. Moreover, THB exposure resulted in a list of up-regulated mRNA transcripts that best matched an osteogenic tissue expression signature as compared to other tissue expression signatures archived in several databases. To determine whether oral administration of THB resulted in improved skeletal growth, we provided pregnant rats with chow supplemented with THB during pregnancy and lactation. After weaning, offspring received THB continuously until postnatal day 50 (approximately 10 mg kg−1 day−1). Administration of THB resulted in neonates with larger bones and 50 day old offspring accumulated greater body mass, longer and thicker femora and superior tibial trabecular parameters. The accelerated growth did not adversely affect the strength and resilience of the bones. These results indicate that THB increases the osteogenic potential of bone marrow osteoprogenitors, and dietary supplementation of a safe dose of THB to expectant mothers and during the postnatal period could accelerate skeletal development in their offspring.

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“…Western blot analysis. Western blot analysis was performed by a modification of the technique described previously (Jang et al, 2015). Whole cell lysates were prepared by lysing cells in lysis buffer (150 mM NaCl, 2 mM EDTA, 1% NP-40, 0.5% sodium deoxycholate, 0.1% SDS, 50 mM Tris-Cl, 1 mM phenylmethylsulfonyl fluoride).…”

Section: Measurement Of Immunoglobulin E and Cytokine Levelmentioning

confidence: 99%

Ramalin Isolated from Ramalina Terebrata Attenuates Atopic Dermatitis‐like Skin Lesions in Balb/c Mice and Cutaneous Immune Responses in Keratinocytes and Mast Cells

Park

Jang

Yim

et al. 2016

Phytotherapy Research

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Atopic dermatitis (AD) is a chronic inflammatory skin disease that involves eczematous skin lesions with pruritic erythematous papules. In this study, we investigated the mitigating effects of ramalin, a component of the Antarctic lichen Ramalina terebrata against AD in vivo and in vitro. Oral administration of ramalin lessened scratching behaviors and significantly reduced both serum immunoglobulin E and IL-4 levels, and mRNA levels of IL-4 and IL-10 in AD-induced Balb/c mice. In vitro, treatment with ramalin produced significantly less inflammatory chemokines and cytokines, including TARC, MCP-1, RANTES, and IL-8 in TNF-α-stimulated HaCaT cells. In addition, ramalin inhibited the activation of nuclear factor-kappa B as well as the phosphorylation of mitogen-activated protein kinases (MAPK). Furthermore, ramalin treatment resulted in decreased production of β-hexosaminidase and proinflammatory cytokines IL-4, IL-6, and TNF-α in 2,4 dinitrophenyl-human serum albumin-stimulated RBL-2H3 cells through blocking MAPK signaling pathways. The results suggest that ramalin modulates the production of immune mediators by inhibiting the nuclear factor-kappa B and MAPK signaling pathways. Taken together, ramalin effectively attenuated the development of AD and promoted the mitigating effects on Th2 cell-mediated immune responses and the production of inflammatory mediators in mast cells and keratinocytes. Thus, ramalin may be a potential therapeutic agent for AD. Copyright © 2016 John Wiley & Sons, Ltd.

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Theobromine inhibits differentiation of 3T3-L1 cells during the early stage of adipogenesis via AMPK and MAPK signaling pathways

Cited by 70 publications

References 45 publications

Ezetimibe ameliorates lipid accumulation during adipogenesis by regulating the AMPK–mTORC1 pathway

Ezetimibe ameliorates lipid accumulation during adipogenesis by regulating the AMPK–mTORC1 pathway

Theobromine Upregulates Osteogenesis by Human Mesenchymal Stem Cells In Vitro and Accelerates Bone Development in Rats

Ramalin Isolated from Ramalina Terebrata Attenuates Atopic Dermatitis‐like Skin Lesions in Balb/c Mice and Cutaneous Immune Responses in Keratinocytes and Mast Cells

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